Ferroptosis is a novel regulated cell death characterized by excessive membrane lipid peroxidation in an iron- and ROS-dependent manner, which is increasingly recognized for its role in tumor suppression and overcoming therapy resistance in various cancers. Induction of ferroptosis has been shown to sensitize cancer cells to chemotherapy, targeted therapy, and immunotherapy, thereby providing a novel strategy to tumor therapy. Peroxiredoxin 1 (PRDX1), an antioxidant enzyme, regulates redox homeostasis and is involved in tumor invasion, metastasis and prognosis. Increasing evidence suggests that PRDX1 is a negative regulator of ferroptotic cell death. Hence, regulating ferroptosis, via targeting PRDX1 and regulating PRDX1' function, holds promise for the treatment of tumors. In this review, we comprehensively summarized the regulatory of PRDX1 on ferroptosis and discussed the potential of PRDX1-mediated ferroptosis on tumor therapy, aiming to provide a distinct method for finding potential targets to enhance the effectiveness of ferroptosis-based tumor treament.